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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Added by celine.gongora
Last modified by standudu
Group name EquipeCG
Item Type Journal Article
Title Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes
Creator Ragulan et al.
Author Chanthirika Ragulan
Author Katherine Eason
Author Elisa Fontana
Author Gift Nyamundanda
Author Noelia Tarazona
Author Yatish Patil
Author Pawan Poudel
Author Rita T. Lawlor
Author Maguy Del Rio
Author Si-Lin Koo
Author Wah-Siew Tan
Author Francesco Sclafani
Author Ruwaida Begum
Author Larissa S. Teixeira Mendes
Author Pierre Martineau
Author Aldo Scarpa
Author Andrés Cervantes
Author Iain Beehuat Tan
Author David Cunningham
Author Anguraj Sadanandam
Abstract Previously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol. The assay included a reduced 38-gene panel that was selected using an in-house machine-learning pipeline. We applied NanoCRCA to 413 samples from 355 CRC patients. From the fresh frozen samples (n?=?237), a subset had matched microarray/RNAseq profiles (n?=?47) or formalin-fixed paraffin-embedded (FFPE) samples (n?=?58). We also analyzed a further 118 FFPE samples. We compared the assay results with the CMS classifier, different platforms (microarrays/RNAseq) and gene-set classifiers (38 and the original 786 genes). The standard and modified protocols showed high correlation (>?0.88) for gene expression. Technical replicates were highly correlated (>?0.96). NanoCRCA classified fresh frozen and FFPE samples into all five CRCA subtypes with consistent classification of selected matched fresh frozen/FFPE samples. We demonstrate high and significant subtype concordance across protocols (100%), gene sets (95%), platforms (87%) and with CMS subtypes (75%) when evaluated across multiple datasets. Overall, our NanoCRCA assay with further validation may facilitate prospective validation of CRC subtypes in clinical trials and beyond.
Publication Scientific Reports
Volume 9
Issue 1
Pages 7665
Date May 21, 2019
Journal Abbr Sci Rep
Language eng
DOI 10.1038/s41598-019-43492-0
ISSN 2045-2322
Library Catalog PubMed
Extra 00000 PMID: 31113981 PMCID: PMC6529539
Tags original
Date Added 2019/10/10 - 10:40:47
Date Modified 2019/10/22 - 15:20:42
Notes and Attachments PubMed entry (Attachment)
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